This Mentored Research Scientist Development (K01) Award will support the training and career development of a junior investigator with prior training in neuroscience and engineering, transitioning into the field of meditation brain imaging research. The proposed career development plan includes training in mind-body medicine, clinical trials, mental health, neuroimaging, and meditation-based interventions for clinical applications. The proposed research focuses on the neural and physiological mechanisms of mindfulness-based cognitive therapy (MBCT), an effective group intervention for major depressive disorder (MDD). MDD is characterized by maladaptive rumination-a persistence of negative, self-focused mind states. The MBCT framework holds that ruminative tendencies can be remediated by using mindfulness practice to facilitate an earlier recognition of unpleasant mind states and internal feelings that usually trigger rumination, thereby enabling disengagement from the subsequent downward spiral into negative moods typical of MDD. Previous studies (including recent work by the Applicant) suggest that mindfulness-based interventions have measurable effects on brain structure and function, especially in brain regions known to be dysfunctional in MDD, and that meditation training may improve autonomic regulation of cardiorespiratory function, as assessed with measures of heart rate variability (HRV). However, the specific mechanisms of action of MBCT in MDD are currently unknown. In this study we will use functional magnetic resonance imaging (fMRI) and autonomic (HRV) assessments (i) to investigate the longitudinal effects of MBCT on the brain networks involved with interceptive awareness and rumination and on the autonomic nervous system, and (ii) to test the proposed mechanism that increased interceptive brain activation after MBCT improves participant ability to disengage from ruminative brain activity, thereby reducing depressive symptoms. The findings from the proposed research will shed light on the neural and physiological mechanisms of action of MBCT in major depression.